Potassium permanganate resistant amyloid in fine-needle aspirate of the liver

A case of primary amyloidosis, initially detected by fine-needle aspiration of the liver, is reported here. Amorphous acellular metachromatic material was seen extracellularly in between the hepatocytic cords compressing them. This material showed typical apple-green birefringence under crossed bipolars after alkaline Congo-red staining proved its amyloid nature. It was resistant to potassium permanganate pretreatment, indicating it to be of the AL type. © 1994 Wiley-Liss, Inc.     

Cytopathology of uncommon malignant renal neoplasms in the pediatric age group

Malignant renal neoplasms are common solid tumors in pediatric oncology practice. These include the common Wilms' tumor/nephroblastoma and the uncommon neoplasms such as clear-cell sarcoma of the kidney (CCSK), rhabdoid tumor, renal-cell carcinoma, and others. The aim of this study was to describe in detail the cytopathological features of the histopathologically proven uncommon pediatric renal tumors. Aspirates from Wilms' tumor, which are mesenchyme predominant, show clusters of spindle cells associated with the matrix material. Evidence of rhabdomyoblastic differentiation may be present. CCSK, classic subtype, is characterized by round to oval cells arranged perivascularly and also in sheets and clusters intimately associated with a metachromatic matrix mucopolysaccharide material better appreciated in May-Grunwald-Giemsa (MGG)-stained smears. The cells also have more abundant cytoplasm and may show nuclear grooves. Spindle-cell pattern of CCSK is difficult to diagnose on aspiration cytology. Renal-cell carcinoma of childhood shows similar cytological features as its adult counterpart. Rhabdoid tumor of the kidney is characterized by a monomorphic population of cells with abundant cytoplasm, eccentric nuclei with prominent nucleoli. Intrarenal yolk sac tumor is a rare neoplasm and shows severely pleomorphic cells on aspiration.Awareness of these entities is important for the practicing cytopathologist. Further, non-Wilms' renal malignant neoplasms must be distinguished from the common Wilms' tumor so that appropriate chemotherapy protocols may be instituted in cases where the tumor is in an advanced stage of malignancy.     

Evaluation of antifungal susceptibility and clinical characteristics in fungal keratitis in a tertiary care center in North India

Purpose:To study the antifungal susceptibility of common corneal pathogenic fungi to antifungal agents in the North Indian population.Methods:Prospective study of the antifungal sensitivity testing (natamycin, amphotericin B, voriconazole, itraconazole, fluconazole, posaconazole, caspofungin, micafungin) of fungal isolates from 50 cases of culture positive fungal keratitis by using E test method. Details noted included demographic data, visual acuity, clinical details, grade of keratitis, healing time, and success in medical management.Results:Of 50 patients with fungal keratitis (mean age: 40.28 ± 16.77 years), 12 eyes healed within 3 weeks, 14 had a delayed healing response, and 24 had chronic keratitis. Among the 15 cases of Fusarium isolates, 93.3% were sensitive to natamycin, while 40% to amphotericin B; 66.6% to voriconazole, 13.4% to itraconazole and fluconazole each. 80% of Fusarium cases (n = 12) showed susceptibility to posaconazole. Among Aspergillus flavus isolates, 53.4% (n = 8) were sensitive to natamycin, with only 40% (n = 7) showing sensitivity to amphotericin B and good susceptibility to azoles. MIC against susceptible Fusarium spp. for natamycin was 3–16 µg/mL, amphotericin B: 1–8 µg/mL, voriconazole: 0.5–1.5 µg/mL, itraconazole: 0.5–12 µg/mL, posaconazole: 0.094–1.5 µg/mL. MIC against Aspergillus flavus was natamycin: 8–32 µg/mL, amphotericin B: 0.5–16 µg/mL, voriconazole: 0.025–4 µg/mL, itraconazole: 0.125–8 µg/mL, posaconazole: 0.047–0.25 µg/mL; against Aspergillus niger isolates, to natamycin was 6 µg/mL (n=1), amphotericin B 8–12 µg/mL (n = 3), voriconazole: 0.125–0.19 µg/mL (n = 3), itraconazole: 0.38–0.75 µg/mL, posaconazole: 0.064–0.19 µg/mL and against Aspergillus fumigatus (n = 1), was natamycin4 µg/mL, amphotericin B - 8 µg/mL, voriconazole 0.25 µg/mL, itraconazole 1 µg/mL, and posaconazole 0.19 µg/mL. MIC against susceptible Acremonium spp. for natamycin was 1.5–16 µg/mL, amphotericin B: 0.5–8 µg/mL, voriconazole: 0.19–3 µg/mL, itraconazole: 0.125 µg/mL, posaconazole: 0.125–0.5 µg/mL and against susceptible Curvularia was natamycin 0.75–4 µg/mL, amphotericin B 0.5–1 µg/mL, voriconazole 0.125–0.19 µg/mL, itraconazole 0.047–0.094 µg/mL, posaconazole 0.047–0.094 µg/mL. MIC against Mucor spp.+ Rhizopus spp. (n = 1) was natamycin: 8 µg/mL, amphotericin B: 0.75 µg/mL, posaconazole: 1.5 µg/mL. MIC against of Alternaria (n = 1) was voriconazole: 0.19 µg/mL, posaconazole: 0.094 µg/mL. MIC against Penicillium (n=1) was natamycin: 8 µg/mL, voriconazole: 0.25 µg/mL, itraconazole: 0.5 µg/mL, and Posaconazole: 0.125 µg/mL.Conclusion:Our observations highlight the variations in susceptibility to antifungal agents. Posaconazole seems to be effective with low MIC against common corneal pathogenic fungal isolates.     

Gaps and opportunities in the treatment of relapsed-refractory multiple myeloma: Consensus recommendations of the NCI Multiple Myeloma Steering Committee

A wide variety of new therapeutic options for Multiple Myeloma (MM) have recently become available, extending progression-free and overall survival for patients in meaningful ways. However, these treatments are not curative, and patients eventually relapse, necessitating decisions on the appropriate choice of treatment(s) for the next phase of the disease. Additionally, an important subset of MM patients will prove to be refractory to the majority of the available treatments, requiring selection of effective therapies from the remaining options. Immunomodulatory agents (IMiDs), proteasome inhibitors, monoclonal antibodies, and alkylating agents are the major classes of MM therapies, with several options in each class. Patients who are refractory to one agent in a class may be responsive to a related compound or to a drug from a different class. However, rules for selection of alternative treatments in these situations are somewhat empirical and later phase clinical trials to inform those choices are ongoing. To address these issues the NCI Multiple Myeloma Steering Committee formed a relapsed/refractory working group to review optimal treatment choices, timing, and sequencing and provide recommendations. Additional issues considered include the role of salvage autologous stem cell transplantation, risk stratification, targeted approaches for genetic subsets of MM, appropriate clinical trial endpoints, and promising investigational agents. This report summarizes the deliberations of the working group and suggests potential avenues of research to improve the precision, timing, and durability of treatments for Myeloma.Subject terms: Combination drug therapy, Cancer therapeutic resistance, Targeted therapies     

Tear film lipid layer thickness measurement from Ocular Surface Analyzer as a marker to monitor treatment of meibomian gland dysfunction in a study comparing physiological detergent-free eyelid wipes with conventional therapy: A randomized trial

Purpose:To compare the efficacy of physiological, non-detergent eyelid wipes with conventional lid hygiene in patients with meibomian gland dysfunction (MGD).Methods:Fifty participants with MGD were recruited and randomized into two groups. Participants in group I used Evolve Pure™ Eyewipes twice a day to clean the eyelid debris along with standard therapy (antibiotic and lubricants) and participants in group II followed lid hygiene with warm compresses along with standard therapy. Symptoms, ocular surface assessment (lipid layer thickness, tear meniscus height, non-invasive tear film breakup time, and meibography), slit-lamp biomicroscopy (eyelash contamination, meibomian gland blockage, meibomian gland secretion, and meibomian gland telangiectasia) and tear film osmolarity were noted at baseline and 90 days after therapy.Results:Significant improvement in symptoms and signs of MGD was observed in both groups after treatment (P < 0.001); however, the clinical improvement was better with the use of eyelid wipes. Lipid layer thickness increased significantly in group I (P = 0.0006) and group II (P = 0.0002), which was maintained even after adjusting for sociodemographic variables such as age, sex, and severity score of symptoms and signs.Conclusion:Lipid layer thickness of the tear film is a sensitive marker in monitoring response to treatment in patients with MGD. The use of physiological detergent-free eyelid wipes is non-inferior to lid hygiene and warm compresses, which remains the mainstay for treatment of MGD; the clinical improvement with eyelid wipes was noted to be better.     

CD40 activation mediates p53-dependent cell cycle regulation in human multiple myeloma cell lines

It has been reported that the activation of multiple myeloma (MM) cells by CD40 induces proliferation, growth arrest, and apoptosis. To determine whether the biologic sequelae of CD40 activation in MM cells depends on p53 function, we identified temperature-sensitive p53 mutations in the RPMI 8226 (tsp53E285K) and the HS Sultan (tsp53Y163H) MM cell lines. These cells were then used as a model system of inducible wtp53-like function because wild-type-like p53 is induced at permissive (30 degrees C) but not at restrictive (37 degrees C) temperatures. Using p21-luciferase reporter assays, we confirmed that CD40 induces p53 transactivation in RPMI 8226 and HS Sultan cells cultured under permissive, but not restrictive, conditions. Furthermore, CD40 activation of these MM cells under permissive, but not restrictive, temperatures increased the expression of p53 and p21 mRNA and protein. Importantly, CD40 activation induced the proliferation of RPMI 8226 and HS Sultan cells at restrictive temperatures and growth arrest and increased subG1 phase cells at permissive temperatures. These data confirmed that CD40 activation might have distinct biologic sequelae in MM cells, depending on their p53 status.     

Ricolinostat (ACY‐1215) induced inhibition of aggresome formation accelerates carfilzomib‐induced multiple myeloma cell death

Proteasome inhibition induces the accumulation of aggregated misfolded/ubiquitinated proteins in the aggresome; conversely, histone deacetylase 6 (HDAC6) inhibition blocks aggresome formation. Although this rationale has been the basis of proteasome inhibitor (PI) and HDAC6 inhibitor combination studies, the role of disruption of aggresome formation by HDAC6 inhibition has not yet been studied in multiple myeloma (MM). The present study aimed to evaluate the impact of carfilzomib (CFZ) in combination with a selective HDAC6 inhibitor (ricolinostat) in MM cells with respect to the aggresome‐proteolysis pathway. We observed that combination treatment of CFZ with ricolinostat triggered synergistic anti‐MM effects, even in bortezomib‐resistant cells. Immunofluorescent staining showed that CFZ increased the accumulation of ubiquitinated proteins and protein aggregates in the cytoplasm, as well as the engulfment of aggregated ubiquitinated proteins by autophagosomes, which was blocked by ricolinostat. Electron microscopy imaging showed increased autophagy triggered by CFZ, which was inhibited by the addition of ACY‐1215. Finally, an in vivo mouse xenograft study confirmed a decrease in tumour volume, associated with apoptosis, following treatment with CFZ in combination with ricolinostat. Our results suggest that ricolinostat inhibits aggresome formation, caused by CFZ‐induced inhibition of the proteasome pathway, resulting in enhanced apoptosis in MM cells.     

Non‐Hodgkin's lymphoma presenting as breast masses: A series of 10 cases diagnosed on FNAC

Primary breast lymphoma (PBL) is a rare disease, which comprises 0.04–0.53% of all primary malignant tumors of the breast. The most frequent histological subtype is diffuse large B‐cell type (DLBCL) (40–70%). Differentiation of PBLs from other breast tumors such as poorly differentiated carcinomas and lobular carcinoma may at times be difficult on cytomorphology alone. An audit of breast lymphomas diagnosed on fine needle aspiration cytology (FNAC) over a period of 9 years (2001–2009) was performed. Ten cases were retrieved and the cytomorphology was reviewed along with immunochemistry (IHC), flow cytometry as well as histopathology, wherever available. The age of patients ranged from 17 to 83 years. Eight cases were diagnosed as non‐Hodgkin's lymphoma, high‐grade on FNAC. Histopathology was available in four of these cases and cell block was available in one case. Lymphoid cells were positive for leukocyte‐common antigen (LCA) and CD20 and negative for CD3 in these cases. The same was confirmed by flow cytometry on aspirated material in one case. A diagnosis of DLBCL was offered in these five cases. One case was a low‐grade NHL and another case was a young male, a known case of acute leukemia and had leukemic infiltration in the breast lump. We wish to emphasize the potential importance of FNAC in breast lymphoma and the same can be helpful to avoid unnecessary surgery in these cases. The differential diagnostic entities have been discussed. IHC and flow cytometry can be performed on the aspirated material and provide valuable information. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.